The principal objective of our work is to define the possible role of nonenzymatic glycosylation and browning in causing the complications associated with diabetes mellitus. The reaction, which is occurring in normal individuals, proceeds at a more rapid rate in the diabetic patient. Studies in the nonenzymatic glycosylation of hemoglobin have given both a practical tool for assessing the control of diabetic patients and insight into the biochemical events that might lead to pathological changes. We have recently extended these studies to the ocular lens where we have also found evidence of nonenzymatic glycosylation of proteins. It appears that these glycosylated proteins are more susceptible to sulfhydryl oxidation and form high molecular weight aggregates. These aggregates eventually attain a size greater than 50 million and can scatter light. We have recently proposed that this might in fact be a mechanism for cataract formation. In addition, we have presented evidence that the nonenzymatic glycosylated proteins can undergo further rearrangements to form brown pigments in a manner analogous to that described previously by food chemists. In addition to forming yellow-brown pigments, these rearrangement products can act as cross-links to lens proteins also giving high molecular weight aggregates. We have already described a new method for the isolation of glycosylated amino acids and peptides from complex biological material. This method has proved applicable to studies of urine as a means of monitoring diabetic control as well as the amount of glycosylation of myelin proteins in diabetic animals. In the coming year, we propose to study to further elucidate the structure of the nonenzymatic browning product that occurs in senile cataracts as well as study the relationship of non-enzymatic glycosylation and browning products to cataract formation and peripheral neuropathy.